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GENETICS OF HYPOPLASTIC LEFT HEART SYNDROME

Part of: Bespoke shallow archive Weizmann

Published online by Cambridge University Press:  01 May 2007

HELEN COX  and
DAVID I WILSON
HELEN COX*
Affiliation:
Clinical Genetics Unit, Birmingham Women's Hospital, Birmingham
DAVID I WILSON
Affiliation:
Human Genetics, The Duthie Building (MP808) Southampton General Hospital, Tremona Road, Southampton SO16 6YD
*
Helen Cox, Clinical Genetics Unit, Birmingham Women's Hospital, Metchley Park Road, Edgbaston, Birmingham B15 2TG.
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Extract

The aetiology of hypoplastic left heart syndrome (HLH) is complex and involves both genetic and environmental factors. Hypoplastic left heart syndrome accounts for 1.4–3.8% of all congenital heart defects but up to 25% of neonatal deaths. As well as having a high mortality, HLH is a very significant cause of morbidity and therefore justifies aetiological investigation.

Type
Research Article
Information
Fetal and Maternal Medicine Review , Volume 18 , Issue 2 , May 2007 , pp. 103 - 119
Copyright
Copyright © Cambridge University Press 2007

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References

REFERENCES

1Lang, PD, Fyler, DC. Hypoplastic left heart syndrome, mitral atresia and aortic atresia. In: Fyler, DC, (ed) Nadasi Paediatric Cardiology Hanley & Belfus 1992; 623–624.Google Scholar
2Chang, R-KR, Chen, AY, Klitzner, TS. Clinical Management of infants with Hypoplastic Left Heart Syndrome in the United States, 1988–1997. Pediatrics 2002; 110: 292–98.CrossRefGoogle ScholarPubMed
3Noonan, JA, Nadas, AS. The hypoplastic left heart syndrome. An analysis of 101 cases. Pediatr Clin North Am 1958; 5: 1029–1056.CrossRefGoogle ScholarPubMed
4Tchervenkov, CI, Jacobs, ML, Tahta, SA. Congenital heart surgery nomenclature and database project: Hypoplastic left heart syndrome. Ann Thorac Surg 2000; 69: S170–79.CrossRefGoogle ScholarPubMed
5Brownell, LG, Shokeir, MHK. Inheritance of hypoplastic left heart syndrome (HLHS); Further observations. Clin Genet 1976; 9: 245–49.CrossRefGoogle ScholarPubMed
6Morris, CD, Outcalt, J, Menashe, VD. Hypoplastic left heart syndrome: natural history in a geographically defined population. Pediatrics 1990; 85: 977–83.CrossRefGoogle Scholar
7Hoffman, JIE, Kaplan, S. The incidence of congenital heart disease. JACC 2002; 39: 1890–1900.CrossRefGoogle ScholarPubMed
8Tikkanen, J, Heinonan, OP. Risk factors for hypoplastic left heart syndrome. Teratology 1994; 50: 112–17.CrossRefGoogle ScholarPubMed
9Grech, V. Decreased prevalence of hypoplastic left heart syndrome in Malta. Paediatr Cardiol 1999; 20: 355–57.CrossRefGoogle ScholarPubMed
10Cerboni, P, Robillard, PY, Hulsey, TC, Sibille, G, Ngyuen, J. Congenital heart disease diagnosed in Guadaloupe. Bull Pan Am Health Organ 1993; 27: 151–53.Google Scholar
11Andrews, R, Tulloh, R, Sharland, G, Simpson, J, Rollings, S, Baker, E et al. Outcome of staged reconstructive surgery for hypoplastic left heart following antenatal diagnosis. Arch Dis Child 2001; 85: 450–51.CrossRefGoogle ScholarPubMed
12Hoshino, K, Ogawa, K, Hishitani, T, Kitazawa, R, Uehara, R. Hypoplastic Left Heart Syndrome: duration of survival without surgical intervention. Am Heart J 1999; 137: 535–42.CrossRefGoogle ScholarPubMed
13Norwood, WI, Kirklin, JK, Sanders, SP. Hypoplastic Left Heart Syndrome: Experience with palliative surgery. Am J Cardio 1980; 45: 87–91.CrossRefGoogle ScholarPubMed
14Norwood, WI. Hypoplastic Left Heart Syndrome. Ann Thorac Surg 1991; 52: 688–95.CrossRefGoogle ScholarPubMed
15Fraser, CD, Mee, RBB. Modified Norwood procedure for hypoplastic left heart syndrome. Ann Thorac Surg 1995; 60: 546–49.CrossRefGoogle ScholarPubMed
16Kishimoto, H, Kawahira, Y, Kawata, H, Miura, T, Iwai, S, Mori, T. The modified Norwood palliation on a beating heart. J Thorac Cardiovasc Surg 1999; 118: 1130–132.CrossRefGoogle ScholarPubMed
17Pizarro, C, Malec, E, Maher, KO, Januszewska, K, Gidding, SS, Murdison, KA et al. Right ventricle to pulmonary artery conduit improves outcome after stage I Norwood for hypoplastic left heart syndrome. Circulation 2003; 108: II–155.CrossRefGoogle Scholar
18Razzouk, AJ, Chinnock, RE, Gundry, SR, Johnston, JK, Larsen, RL, Baum, MF et al. Transplantation as a primary treatment for hypoplastic left heart syndrome: Intermediate-term results. Ann Thorac surg 1996; 62: 1–8.CrossRefGoogle ScholarPubMed
19Turrentine, MW, Kesler, KA, Caldwell, R, Darragh, R, Means, L, Mahomed, Y et al. Cardiac transplantation in infants and children. Ann Thorac Surg 1994; 58: 1664–669.Google Scholar
20Wenstrom, KD, Johanning, GL, Johnston, KE, DuBard, M. Association of the C677T methylenetetrahydrofolate reductase mutation and elevated homocysteine levels with congenital cardiac malformations. Am J Obstet Gynecol 2001; 184: 806–12.CrossRefGoogle ScholarPubMed
21McBride, KL, Fernbach, S, Menesses, A, Molinari, L, Quay, E, Pignatelli, R et al. A family-based association study of congenital left-sided heart malformations and 5,10 methylenetetrahydrofolate reductase. Birth Defect Res A 2004; 70: 825–30.CrossRefGoogle Scholar
22Wilson, PD, Loffredo, CA, Correa-Villaseñor, , Ferencz, C. Attributable fraction for cardiac malformations. Am J Epidemiol 1998; 148: 414–23.CrossRefGoogle ScholarPubMed
23Ferencz, C, Correa-Villasenor, A, Loffredo, CA, Wilson, PD. Genetic and environmental risk factors of major cardiovascular malformations: the Baltimore-Washington infant study: 1981–1989. In: Perspect Paediatr Cardiol, Vol 5, Armonk, NY: Futura Publ Co, Inc, 1997.Google Scholar
24Loffredo, CA, Wilson, PD, Ferencz, C. Maternal diabetes: an independent risk factor for major cardiovascular malformations with increased mortality of affected infants. Teratology 2002; 64: 98–106.CrossRefGoogle Scholar
25Winter, RM, Baraitser, M. London Dysmorphology Database version 2.10 1998 Oxford University Press.Google Scholar
26Harh, JY, Paul, MH, Gallen, WJ, Friedberg, DZ, Kaplan, S. Experimental production of hypoplastic left heart in the chick embryo. Am J Cardiol 1973; 31: 51–56.CrossRefGoogle ScholarPubMed
27Lev, M. Pathological anatomy and interrelationship of hypoplasia of the aortic tract complex. Lab Invest 1952; 1: 61–70.Google Scholar
28Sherman, FE. An Atlas of Congenital Heart Disease. Philadelphia, Lea and Febiger, 1963; 229–34.Google Scholar
29Nora, JJ, Nora, AH. The genetic contribution to CHD. In: Nora, JJ and Takas, A, (eds.) CHD: Causes and Processes. London, England: Futura Publishing Co. Inc; 1984.Google Scholar
30Brenner, JA, Berg, KA, Schneider, DS, Clark, EB, Boughman, JA. Cardiac malformations in relatives of infants with hypoplastic left heart syndrome. AJDC 1989; 143: 1492–495.Google ScholarPubMed
31Burn, J, Brennan, P, Little, J, Holloway, S, Coffey, R, Somerville, J et al. Recurrence risks in offspring of adults with major heart defects: results from first cohort of British collaborative study. Lancet 1998; 351: 311–16.CrossRefGoogle ScholarPubMed
32Boughman, JA, Berg, KA, Astemborski, JA, Clark, EB, McCarter, RJ, Rubin, JD et al. Familial risks of congenital heart defect assessed in a population-based epidemiologic study. Am J Med Genet 1987; 26: 839–49.CrossRefGoogle Scholar
33Loffredo, CA, Chokkalingam, A, Sill, AM, Boughman, JA, Clark, EB, Scheel, J et al. Prevalence of congenital cardiovascular malformations among relatives of infants with hypoplastic left heart, coarctation of the aorta, and d-transposition of the great arteries. Am J Med Genet 2004; 124A: 225–30.CrossRefGoogle ScholarPubMed
34Anderson, RC. Congenital cardiac malformations in 109 sets of twins and triplets. Am J Cardiol 1977; 39: 1045–1050.CrossRefGoogle ScholarPubMed
35Verheijen, PM, Lisowski, LA, Plantinga, RF, Hitchcock, JF, Bennink, GBWE, Stoutenbeek, P et al. Prenatal diagnosis of the fetus with hypoplastic left heart syndrome. Herz 2003; 28: 250–56.CrossRefGoogle ScholarPubMed
36Shokeir, MHK. Hypoplastic left heart syndrome; An autosomal recessive disorder. Clin Genet 1971; II: 7–14.CrossRefGoogle Scholar
37Gerboni, S, Sabatino, G, Mingarelli, R, Dallapiccola, B. Coarctation of the aorta, interrupted aortic arch, and hypoplastic left heart syndrome in three generations. J Med Genet 1993; 30: 328–29.CrossRefGoogle ScholarPubMed
38Wessels, MW, Berger, RM, Frohn-Mulder, IM, Roos-Hesselink, JW, Hoogeboom, JJ, Mancini, GS et al. Autosomal dominant inheritance of left ventricular outflow tract obstruction. Am J Med Genet 2005; 134: 171–79.CrossRefGoogle Scholar
39Keith, JD. Bicuspid aortic valve. In: Keith, JD, Rowe, RD, Vlad, P, eds. Heart Disease in Infancy and Childhood. New York, NY: Macmillan Publishing Co. Inc; 1978: 728–35.Google Scholar
40Natowicz, M, Chatten, J, Clancy, R, Conard, K, Glauser, T, Huff, D et al. Genetic disorders and major extracardiac anomalies associated with the hypoplastic left heart syndrome. Pediatrics 1988; 82: 698–706.CrossRefGoogle ScholarPubMed
41Brackley, KJ, Kilby, MD, Wright, JG, Brawn, WJ, Sethia, B, Stumper, O et al. Outcome after prenatal diagnosis of hypoplastic left heart syndrome: a case series. The Lancet 2000; 356: 1143–147.CrossRefGoogle ScholarPubMed
42Perez-Delboy, A, Simpson, GG. Ultrasound Med Biol 2003; 29: S134.CrossRefGoogle Scholar
43Schinzel, AA. Cardiovascular defects associated with chromosomal aberrations and malformation syndromes. Prog Med Genet 1983; 5: 303–81.Google ScholarPubMed
44Brewer, C, Holloway, S, Zawalnyski, P, Schinzel, A, Fitzpatrick, D. A chromosomal deletion map of human malformations. Am J Hum Genet 1998; 63: 1153–159.CrossRefGoogle ScholarPubMed
45Van Karnebeek, CDM, Hennekam, R. Associations between chromosomal anomalies and congenital heart defects: a database search. Am J Med Genet 1999; 84: 158–66.3.0.CO;2-5>CrossRefGoogle ScholarPubMed
46Phillips, H, Renforth, GL, Spalluto, C, Hearn, T, Curtis, ARJ, Craven, L et al. Narrowing the critical region within 11q24-qter for hypoplastic left heart and identification of a candidate gene JAM3, expressed during cardiogenesis. Genomics 2002; 79: 475–78.CrossRefGoogle ScholarPubMed
47Saneto, RP, Applegate, KE, Frankel, DG. Atypical manifestations of 2 cases of trisomy 9 syndrome: rethinking developmental delay. Am J Med Genet 1998; 80: 42–45.3.0.CO;2-S>CrossRefGoogle Scholar
48Morrissette, JJ, Laufer-Cahana, A, Medne, L, Russell, KL, Venditti, CP, Kline, R et al. Patient with trisomy 9p and a hypoplastic left heart with a tricentric chromosome 9. Am J Med Genet 2003; 123A: 279–84.CrossRefGoogle Scholar
49Qazi, QH, Kanchanapoomi, R, Cooper, R, Madahar, C, Beller, E. Dup(12p) and hypoplastic left heart. Am J Med Genet 1981; 9: 195–99.CrossRefGoogle ScholarPubMed
50Chen, CP, Chern, SR, Hsu, CY, Lee, CC, Lee, MS, Wang, W. Prenatal diagnosis of de novo partial trisomy 13q (13q22–>qter) and partial monosomy 8p (8p23.3–>pter) associated with holoprosencephaly, premaxillary agenesis, hexadactyly and hypoplastic left heart. Prenat Diagn 2005; 25: 334–36.CrossRefGoogle Scholar
51Bacino, CA, Lee, B, Spikes, AS, Shaffer, LG. Trisomy 16q in a female newborn with a de novo X;16 translocation and hypoplastic left heart. Am J Med Genet 1999; 82: 128–31.3.0.CO;2-4>CrossRefGoogle Scholar
52Greally, JM, Neiswanger, K, Cummins, JH, Boone, LY, Lenkey, SG, Wenger, SL et al. A molecular anatomical analysis of mosaic trisomy 16. Hum Genet 1996; 98: 86–90.CrossRefGoogle ScholarPubMed
53Vasquez, JC, Rabah, R, Delius, RE, Walters, HL. Hypoplastic left heart syndrome with intact atrial septum associated with deletion of the short arm of chromosome 18. Cardiovasc Pathol 2003; 12: 102–104.CrossRefGoogle ScholarPubMed
54Gu, H, Yeboa, K, Warburton, D, Tubo, T, Dhuper, S, Delpreeno, M et al. Hypoplastic left heart in a female infant with trisomy 4q due to a de novo 4;21 translocation. Am J Med Genet 2002; 107: 330–33.Google Scholar
55Theodoropoulos, DS, Cowan, JM, Elias, ER, Cole, C. Physical findings in 21q22 deletion suggest critical region for 21q-phenotype in q22. Am J Med Genet 1995; 59: 161–63.CrossRefGoogle ScholarPubMed
56Witters, I, Moerman, P, Louwagie, D, Van Assche, FA, Migeon, BR, Fryns, JP. Second trimester prenatal diagnosis of epignathus teratoma in ring X chromosome mosaicism with inactive ring X chromosome. Ann Genet 2001; 44: 179–82.CrossRefGoogle ScholarPubMed
57Bruneau, BG, Logan, M, Davis, N, Levi, T, Tabin, CJ, Seidman, JG et al. Chamber-specific cardiac expression of Tbx5 and heart defects in Holt-oram syndrome. Dev Biol 1999; 211: 100–108.CrossRefGoogle ScholarPubMed
58Newbury-Ecob, RA, Leanage, R, Raeburn, JA, Young, ID. Holt Oram syndrome: a clinical genetic study. J Med Genet 1996; 33: 300–307.CrossRefGoogle ScholarPubMed
59Bartsch, O, Wagner, A, Hinkel, GK, Krebs, P, Stumm, M, Schmalenberger, B et al. FISH studies in 45 patients with Rubinstein-Taybi syndrome: deletions associated with polysplenia, hypoplastic left heart and death in infancy. Eur J Hum Genet 1999; 7: 748–56.CrossRefGoogle ScholarPubMed
60Stevens, CA, Bhakta, MG. Cardiac abnormalities in the Rubinstein-Taybi syndrome. Am J Med Genet 1995; 59: 346–48.CrossRefGoogle ScholarPubMed
61Hanauer, D, Argilla, M, Wallerstein, R. Rubinstein-Taybi syndrome and hypoplastic left heart. Am J Med Genet 2002; 112: 109–11.CrossRefGoogle ScholarPubMed
62Garg, V, Muth, AN, Ransom, JF, Schluterman, MK, Barnes, R, King, IN et al. Mutations in NOTCH1 cause aortic valve disease. Nature 2005; 437: 270–74.CrossRefGoogle ScholarPubMed
63Benson, DW, Sharkey, A, Fatkin, D, Lang, P, Basson, CT, McDonough, B et al. Reduced penetrance, variable expressivity, and genetic heterogeneity of familial atrial septal defects. Circulation 1998; 97: 2043–2048.CrossRefGoogle ScholarPubMed
64Schott, JJ, Benson, DW, Basson, CT, Pease, W, Silberbach, GM, Moak, JP et al. Congenital heart disease caused by mutations in the transcription factor NKX2–5. Science 1998; 281: 32–34.CrossRefGoogle ScholarPubMed
65Goldmuntz, E, Geiger, E, Benson, DW. NKX2.5 mutations in patients with tetralogy of fallot. Circulation 2001; 104: 2565–568.CrossRefGoogle ScholarPubMed
66Elliot, DA, Kirk, EP, Yeoh, T, Chandar, S, McKenzie, F, Taylor, P et al. Cardiac homeobox gene NKX2–5 mutations and congenital heart disease. Associations with atrial septal defect and hypoplastic left heart syndrome. JACC 2003; 41: 2072–2076.CrossRefGoogle Scholar
67Bodmer, R. The gene tinman is required for specification of the heart and visceral muscles in Drosophila. Development 1993; 118: 719–29.CrossRefGoogle ScholarPubMed
68Lyons, I, Parsons, LM, Hartley, L, Li, R, Andrews, JE, Robb, L et al. Myogenic and morphogenetic defects in the heart tubes of murine embryos lacking the homeobox gene Nkx-2.5. Genes Dev 1995; 9: 1654–666.CrossRefGoogle Scholar
69Casey, B, Devoto, M, Jones, KL, Ballabio, A. Mapping a gene for familial situs abnormalities to human chromosome Xq24–q27.1. Nat Genet 1993; 5: 403–407.CrossRefGoogle ScholarPubMed
70Ferrero, GB, Gebbia, M, Pilia, G, Witte, D, Peier, A, Hopkin, RJ et al. A submicroscopic deletion of Xq26 associated with familial situs ambiguus. Am J Hum Genet 1997; 61: 395–401.CrossRefGoogle ScholarPubMed
71Gebbia, M, Ferrero, GB, Pilia, G, Bassi, MT, Aylsworth, A, Penman-Splitt, et al. X-linked situs abnormalities result from mutations in ZIC3. Nat Genet 1997; 17: 305–308.CrossRefGoogle ScholarPubMed
72Megarbane, A, Salem, N, Stephan, E, Ashoush, R, Lenoir, D, Delague, V et al. X-linked transposition of the great arteries and incomplete penetrance among males with a mutation in ZIC3. Eur J Hum Genet 2000; 8: 704–708.CrossRefGoogle ScholarPubMed
73Ware, SM, Peng, J, Zhu, L, Fernbach, S, Colicos, S, Casey, B et al. Identification and functional analysis of ZIC3 mutations in heterotaxy and related congenital heart defects. Am J Hum Genet 2004; 74: 93–105.CrossRefGoogle ScholarPubMed
74Brewer, C, Holloway, S, Zawalnyski, P, Schinzel, A, Fitzpatrick, D. A chromosomal duplication map of malformations: regions of suspected haplo- and triplolethality and tolerance of segmental aneuploidy in humans. Am J Hum Genet 1999; 64: 1702–708.CrossRefGoogle ScholarPubMed
75Grossfeld, P. The genetics of hypoplastic left heart syndrome. Cardiol Young 1999; 9: 627–39.CrossRefGoogle ScholarPubMed
76Driscoll, DA, Budarf, ML, Emanuel, BS. A genetic etiology for DiGeorge syndrome: consistent deletions and microdeletions of 22q11. Am J Hum Genet 1992; 50: 924–33.Google ScholarPubMed
77Scambler, PJ, Kelly, D, Lindsay, E, Williamson, R, Goldberg, R, Shprintzen, R et al. Velo-cardio-facial syndrome associated with chromosome 22 deletions encompassing the DiGeorge locus. Lancet 1992; 339: 1138–139.CrossRefGoogle ScholarPubMed
78Wilson, DI, Goodship, JA, Burn, J, Cross, IE, Scambler, PJ. Deletions within chromosome 22q11 in familial congenital heart disease. Lancet 1992; 340; 573–75.CrossRefGoogle ScholarPubMed
79Consevage, MW, Seip, JR, Belchis, DA, Davis, AT, Baylen, BG, Rogan, PK. Association of mosaic chromosomal 22q11 deletion with hypoplastic left heart syndrome. Am J Cardiol 1996; 77: 1023–1025.CrossRefGoogle ScholarPubMed
80Ryan, AK, Goodship, JA, Wilson, DI, Philip, N, Levy, A, Seidel, H et al. Spectrum of clinical features associated with interstitial chromosome 22q11 deletions: a European collaborative study. J Med Genet 1997; 34: 798–804.CrossRefGoogle ScholarPubMed
81Curran, ME, Atkinson, DL, Ewart, AK, Morris, CA, Leppert, MF, Keating, MT. The elastin gene is disrupted by a translocation associated with supravalvular aortic stenosis. Cell 1993; 73: 159–68.CrossRefGoogle ScholarPubMed